Training tomorrow's HIV researchers

With no end yet to the pandemic, a program supports young South African physician-scientists

June 12, 2017•By Mary Engel / Fred Hutch News Service

Dr. Nishila Moodley, left, receives an achievement award from her mentor, Dr. Glenda Gray, before 700 members of the HIV Vaccine Trials Network in Washington, D.C.Photo courtesy of HVTN

When Dr. Nishila Moodley took the stage to receive a special achievement award, 700 scientists, clinicians, outreach specialists and community members attending the annual meeting of the HIV Vaccine Trials Network — the largest global network working to develop and test a preventive HIV vaccine — cheered her accomplishment.

They also celebrated the future of HIV vaccine research in South Africa.

Moodley is the first graduate of the HVTN’s South African HVTN AIDS Vaccine Early Stage Investigator Programme, an initiative to foster a new generation of homegrown HIV researchers. In just three years, and while continuing to work full-time as a physician at the Perinatal HIV Research Unit in Soweto, South Africa, Moodley completed doctoral studies in public health and published five papers on how to roll out a long-hoped-for HIV vaccine when the time comes. She will receive her Ph.D. in early July from the prestigious University of Witwatersrand in Johannesburg.

“This young woman completed her Ph.D. in record time while working full time,” said her mentor, Dr. Glenda Gray, president of the South African Medical Research Council, as she surprised Moodley with the award at the May meeting in Washington D.C. “After a lot of sweat and tears, we managed to get her Ph.D. in before she delivered her second baby.” (Moodley began the program just four months after delivering her first.)

Gray, a co-leader of the HVTN — which is headquartered at Fred Hutchinson Cancer Research Center — and head of its Africa Program, is internationally known for her HIV research, especially on preventing HIV-infected mothers from passing the virus to their newborns. She is one of a handful of HVTN researchers from South Africa who have been involved in the pandemic since its earliest days — and who now worry that there are not enough young physician-scientists in the pipeline who are specializing in HIV.

The pipeline concern is not confined to South Africa or to HIV. A commentary published recently in Clinical Infectious Diseases, the journal of the Infectious Disease Society of America, warned of a shortage of infectious disease specialists in the United States, with 20 percent of ID fellowships at U.S. medical centers going unfilled for 2017, substantially more than other medical subspecialties. One demand among many for ID specialists is the increasing number of people who are now, thanks to antiretroviral treatment, living with HIV.

In sub-Saharan Africa, which has far fewer physicians overall and a far greater number of people with HIV, the imbalance between supply and demand is exponentially greater. South Africa has more people infected with HIV than any other country in the world, and despite recent strides made in getting those infected on treatment, Gray and other experts know that successfully developing a preventive vaccine is critical to ending the epidemic.

“We’re still in the most serious infectious disease outbreak not only of our generation but among the top three or four in history,” said Dr. Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases, which funds the HVTN, at the May meeting. “We absolutely need a vaccine. Anybody who thinks we’re going to end HIV without one doesn’t understand this epidemic.”

The goal: physician-researchers

Moodley understands the epidemic. Lifesaving antiretroviral drugs that transformed AIDS in Western countries in 1996 took more than a decade to reach South Africa. Moodley entered medical school at “a terrible time,” she said.

“You graduate medical school when you’re still very young, you’re still very naïve,” she said. “The death and devastation that you find in the real world is scary.”

She was particularly struck by seeing young women her own age and younger dying. For complex biological, sociological and cultural reasons, young African women are particularly hard hit by HIV/AIDS. In South Africa alone, 2,000 women aged 15 to 25 become infected with HIV every week. More than 100,000 a year die of AIDS.

Instead of feeling daunted by the devastation, Moodley was drawn to help. Soon her interest in HIV expanded to include addressing systemic problems affecting large groups of people rather than treating individual patients. So after finishing her medical degree, she added a master’s in public health. The HVTN early stage investigator program allowed her to go on for a doctorate.

She started her Ph.D. four months after her first son, Kieran, was born. She finished writing her dissertation just before the birth of her second son, James.

Combining work with study while juggling childrearing with her equally busy husband, who is also in academia, “teaches you how to manage your time because you have to manage it,” Moodley said.

Still, she admitted, “I am missing about four or five years of sleep.”

Practicing research as well as medicine can be like holding two — or three or four — full-time jobs, but those who do so strongly believe that each practice informs the other. Clinic experience grounds the researcher in real-world needs and speeds the translation of lifesaving innovations from the bench to the bed.

Most of Moodley’s peers focused on clinical work, not research. Few went on to pursue a Ph.D.

“But with the disease burden that we carry, there needs to be research in place,” she said.

Others in the HVTN agreed.

“While South Africa has strong senior-level HIV researchers, there aren’t sufficient numbers of junior-level researchers being developed behind them,” said Danna Flood, manager of training, evaluation and information technology for the HVTN. Flood worked with HVTN investigators Drs. Jim Kublin and Linda-Gail Bekker to look at barriers to doctors entering research careers. Medical training in South Africa has focused on training primary care doctors because of an overall shortage in that field. While critical to address, one consequence is that medical students now get limited exposure to research and don’t always think of it as career option. Among their study’s recommendations was to provide a clearer path to a research career, including training, mentorship and financial support.

Funded by Fauci’s NIAID and the Fogarty International Center, both part of the National Institutes of Health, and coordinated by the Desmond Tutu HIV Centre at the University of Cape Town, the early-stage investigator program provided a salaried, three-year appointment at an HVTN clinical site, tuition for a concurrent Ph.D. program and support for a mentored research project.

“It wasn’t very realistic to finish in three years,” Flood said. “It’s remarkable that Nishila managed to do it.”

Making a difference

For her Ph.D. project, Moodley focused on modeling the best way to get an HIV vaccine — once one is found to work — to the people who need it.

“It’s never a simple issue, rolling out a vaccine,” said HVTN founder and principal investigator Dr. Larry Corey. “Modelers make a difference in planning public health policy.”

But not everyone was as supportive.

“When I first started this project, I received many rejection letters from journals and conferences,” Moodley said. “Mostly I was asked, ‘What HIV vaccine? That’s crazy.’”

Developing a vaccine against HIV has been challenging. The virus attacks the very immune system that is supposed to protect against it and then mutates too rapidly for any response to keep up. Over the years, more than 100 HIV/AIDS vaccine candidates tested clinically have not made it to late-phase trials. Recent scientific discoveries pointing to a new approach, along with a clinical trial that showed at least partial protection, have renewed hope, however. A late-phase trial is underway now, with results expected by late 2020.

If others dismissed planning ahead for that day as crazy, then “I needed to find a supervisor who’s equally crazy — or visionary — to help me through” such a project, Moodley decided.

She found one in Gray, who, like Corey, believes that plans for implementing vaccination programs need to be laid well in advance.

“Glenda has a sign on her door that says, ‘Well-behaved women never make history,’” Moodley said. “You need someone like that. She’s a visionary. She had no qualms about letting me explore new avenues.”

Concerned about the high rate of HIV infections in young women, Moodley, with Gray’s nudging, modeled a plan to introduce an HIV vaccine in adolescent girls at the same time that they receive an already approved vaccine to protect them against the sexually transmitted human papillomavirus, or HPV, that causes cervical cancer.

“Introducing both of those vaccines together would be an ideal public health initiative, considering that South Africa also has the highest cervical cancer incidence in the world,” Moodley said.

Reaping the benefits

Today, Moodley is working on modeling an even more comprehensive, countrywide implementation plan. In doing so, she aims to makes an economic case for why a vaccine is needed.

To scientists such as Fauci, the need for a vaccine is evident. But not everyone sees the urgency now that antiretroviral treatment has transformed HIV from a certain death sentence to a chronic disease, at least for those who have access to the drugs and can tolerate and adhere to the lifelong treatment.

In addition, countries — whether South Africa or the United States — juggle competing demands when deciding which health initiatives to fund. Other diseases and other medical interventions will be competing with an HIV vaccine.

“You need to prove that there’s bang for the buck, basically,” Moodley said. “You need to show a substantial impact on your health outcomes. The point of the model that we’re developing is to show the effect that an HIV vaccine would have; and how without it, we won’t get a handle on the epidemic.”

Now that she has finished her doctorate — it will be awarded in early July — Moodley is collaborating with a Yale University research group to continue her modeling and working on HIV as well as tuberculosis for the Johannesburg-based Aurum Institute, a nonprofit health organization. A second fellow is slated to graduate soon.

The program “allowed me to super-specialize in health economics, which is not something I’d dealt with before, and to understand vaccinology better and deepen my understanding of epidemiology,” Moodley said. “This was an incredible opportunity.”

Mary Engel is a former staff writer at Fred Hutchinson Cancer Research Center. Previously, she covered medicine and health policy for the Los Angeles Times, where she was part of a team that won a Pulitzer Prize for Public Service. She was also a fellow at the Knight Science Journalism Program at MIT. Follow her on Twitter @Engel140.

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